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SMR-type multidrug resistance pumps
1Department of Biology, University of California at San Diego, La Jolla, CA 92093, USA.
Abstract:
Multidrug resistance (MDR) efflux pumps in pathogenic microorganisms nullify the effects of antimicrobial drugs used in medicine. We have conducted phylogenetic analyses showing that these efflux pumps are associated with five superfamilies of transport systems. One of these, the drug/metabolite transporter (DMT) superfamily includes a family of small multidrug resistance (SMR)-conferring proteins that are discussed in detail in this review. A single microorganism such as Bacillus subtilis may possess multiple homologs of this family, and these homologs are believed to form both homo-oligomeric or hetero-oligomeric pumps, some of which export cationic drugs. The characteristics of some of these systems and the genes that encode them are described, with emphasis on the eight homologs encoded within the B subtilis genome. Anomalies and unanswered questions that provide impetus for future studies are presented.
Insights
Multidrug resistance efflux pumps, particularly the small multidrug resistance (SMR) family, are key to antimicrobial resistance. This review details their structure and function in Bacillus subtilis, highlighting areas for future research.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Multidrug resistance (MDR) efflux pumps are critical in pathogenic microorganisms, reducing the efficacy of antimicrobial drugs.
- These efflux pumps are phylogenetically linked to five superfamilies of transport systems.
Purpose of the Study:
- To review the drug/metabolite transporter (DMT) superfamily, focusing on the small multidrug resistance (SMR) protein family.
- To describe the characteristics and encoding genes of SMR efflux pumps, particularly in Bacillus subtilis.
Main Methods:
- Phylogenetic analyses were employed to classify efflux pump superfamilies.
- Detailed examination of SMR protein homologs within the Bacillus subtilis genome.
Main Results:
- Identified five superfamilies of transport systems associated with MDR efflux pumps.
- Highlighted the SMR family within the DMT superfamily, noting the presence of multiple homologs in Bacillus subtilis.
- Discussed the potential for homo- and hetero-oligomeric pump formation, including those exporting cationic drugs.
Conclusions:
- The SMR family plays a significant role in multidrug resistance.
- Bacillus subtilis possesses eight SMR homologs, contributing to its resistance mechanisms.
- Further investigation into SMR pump anomalies and unanswered questions is crucial for developing new antimicrobial strategies.